Preparation of amorphous valganciclovir hydrochloride

Abstract

The present application relates to processes for the preparation amorphous valganciclovir hydrochloride, comprising combining a solution of valganciclovir with an anti-solvent.

1 . A process for preparing amorphous valganciclovir hydrochloride, comprising:
 a) providing a solution of valganciclovir hydrochloride in a solvent;   b) combining the solution of valganciclovir hydrochloride with an anti-solvent; and   c) isolating a solid from the mixture of b).   
     
     
         2 . The process of  claim 1 , further comprising washing the solid with an anti-solvent. 
     
     
         3 . The process of  claim 1 , further comprising delumping or milling the solid. 
     
     
         4 . The process of  claim 1 , further comprising drying the solid at temperatures less than about 120° C. 
     
     
         5 . The process of  claim 1 , wherein a solvent comprises an alcohol, a glycol, N,N-dimethylformamide, dimethylsulfoxide, N,N-dimethylacetamide, water, or any mixtures thereof. 
     
     
         6 . The process of  claim 1 , wherein a solvent comprises methanol. 
     
     
         7 . The process of  claim 1 , wherein an anti-solvent comprises isopropyl alcohol, 1-propanol, 1-butanol, 2-ethoxymethanol, methyl acetate, ethyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, diethyl ether, methyl t-butyl ether, tetrahydrofuran, toluene, acetonitrile, or any mixtures thereof. 
     
     
         8 . The process of  claim 1 , wherein a solution of valganciclovir hydrochloride is combined with an anti-solvent at about −20° C. to about 50° C. 
     
     
         9 . The process of  claim 1 , wherein combining comprises adding a solution of valganciclovir hydrochloride to an anti-solvent. 
     
     
         10 . The process of  claim 1 , wherein times for combining a solution of valganciclovir hydrochloride with an anti-solvent range from about 10 minutes to about 90 minutes. 
     
     
         11 . The process of  claim 2 , wherein a solid is washed with an anti-solvent comprising isopropyl alcohol, 1-propanol, 1-butanol, 2-ethoxymethanol, methyl acetate, ethyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, diethyl ether, methyl t-butyl ether, tetrahydrofuran, toluene, acetonitrile, or any mixtures thereof. 
     
     
         12 . A process for preparing amorphous valganciclovir hydrochloride, comprising:
 a) providing a solution of valganciclovir hydrochloride in a solvent comprising an alcohol;   b) combining the solution of valganciclovir hydrochloride with an anti-solvent; and   c) isolating a solid from the mixture of b).   
     
     
         13 . The process of  claim 12 , wherein a solvent comprises methanol. 
     
     
         14 . The process of  claim 12 , wherein an anti-solvent comprises isopropyl alcohol, 1-propanol, 1-butanol, 2-ethoxymethanol, methyl acetate, ethyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, diethyl ether, methyl t-butyl ether, tetrahydrofuran, toluene, acetonitrile, or any mixtures thereof. 
     
     
         15 . The process of  claim 12 , wherein an anti-solvent comprises methyl ethyl ketone or isopropyl alcohol. 
     
     
         16 . The process of  claim 12 , wherein a solution of valganciclovir hydrochloride is combined with an anti-solvent at about −20° C. to about 50° C. 
     
     
         17 . The process of  claim 12 , wherein combining comprises adding a solution of valganciclovir hydrochloride to an anti-solvent. 
     
     
         18 . The process of  claim 12 , wherein times for combining a solution of valganciclovir hydrochloride with an anti-solvent range from about 10 minutes to about 90 minutes. 
     
     
         19 . A process for preparing amorphous valganciclovir hydrochloride, comprising:
 a) providing a solution of valganciclovir hydrochloride in a solvent comprising methanol;   b) combining the solution of valganciclovir hydrochloride with an anti-solvent comprising methyl ethyl ketone or isopropanol; and   c) isolating a solid from the mixture of b).